Visual recognition memory: a view from V1

Although work in primates on higher-order visual areas has revealed how the individual and concerted activity of neurons correlates with behavioral reports of object recognition, very little is known about the underlying mechanisms for visual recognition memory. Low-level vision, even as early as primary visual cortex (V1) and even in subjects as unsophisticated as rodents, promises to fill this void. Although this latter approach sacrifices interrogation of many of the most astounding features of visual recognition, it does provide experimental constraint, proximity to sensory input, and a wide range of interventional approaches. The tractability of rodent visual cortex promises to reveal the molecular mechanisms and circuits that are essential for a fundamental form of memory.National Eye Institute (Grant RO1EY023037

Higher brain functions served by the lowly rodent primary visual cortex

It has been more than 50 years since the first description of ocular dominance plasticity-the profound modification of primary visual cortex (V1) following temporary monocular deprivation. This discovery immediately attracted the intense interest of neurobiologists focused on the general question of how experience and deprivation modify the brain as a potential substrate for learning and memory. The pace of discovery has quickened considerably in recent years as mice have become the preferred species to study visual cortical plasticity, and new studies have overturned the dogma that primary sensory cortex is immutable after a developmental critical period. Recent work has shown that, in addition to ocular dominance plasticity, adult visual cortex exhibits several forms of response modification previously considered the exclusive province of higher cortical areas. These "higher brain functions" include neural reports of stimulus familiarity, reward-timing prediction, and spatiotemporal sequence learning. Primary visual cortex can no longer be viewed as a simple visual feature detector with static properties determined during early development. Rodent V1 is a rich and dynamic cortical area in which functions normally associated only with "higher" brain regions can be studied at the mechanistic level.National Eye Institute (Grant RO1 EY023037)National Institute of Mental Health (U.S.) (Grant K99 MH09965

Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities

The discovery of the genetic causes of syndromic autism spectrum disorders and intellectual disabilities has greatly informed our understanding of the molecular pathways critical for normal synaptic function. The top-down approaches using human phenotypes and genetics helped identify causative genes and uncovered the broad spectrum of neuropsychiatric features that can result from various mutations in the same gene. Importantly, the human studies unveiled the exquisite sensitivity of cognitive function to precise levels of many diverse proteins. Bottom-up approaches applying molecular, biochemical, and neurophysiological studies to genetic models of these disorders revealed unsuspected pathogenic mechanisms and identified potential therapeutic targets. Moreover, studies in model organisms showed that symptoms of these devastating disorders can be reversed, which brings hope that affected individuals might benefit from interventions even after symptoms set in. Scientists predict that insights gained from studying these rare syndromic disorders will have an impact on the more common nonsyndromic autism and mild cognitive deficits

GEMINI: A Natural Language System for Spoken-Language Understanding

Gemini is a natural language understanding system developed for spoken language applications. The paper describes the architecture of Gemini, paying particular attention to resolving the tension between robustness and overgeneration. Gemini features a broad-coverage unification-based grammar of English, fully interleaved syntactic and semantic processing in an all-paths, bottom-up parser, and an utterance-level parser to find interpretations of sentences that might not be analyzable as complete sentences. Gemini also includes novel components for recognizing and correcting grammatical disfluencies, and for doing parse preferences. This paper presents a component-by-component view of Gemini, providing detailed relevant measurements of size, efficiency, and performance.Comment: 8 pages, postscrip

Mutations causing syndromic autism define an axis of synaptic pathophysiology

Tuberous sclerosis complex and fragile X syndrome are genetic diseases characterized by intellectual disability and autism. Because both syndromes are caused by mutations in genes that regulate protein synthesis in neurons, it has been hypothesized that excessive protein synthesis is one core pathophysiological mechanism of intellectual disability and autism. Using electrophysiological and biochemical assays of neuronal protein synthesis in the hippocampus of Tsc2+/− and Fmr1−/y mice, here we show that synaptic dysfunction caused by these mutations actually falls at opposite ends of a physiological spectrum. Synaptic, biochemical and cognitive defects in these mutants are corrected by treatments that modulate metabotropic glutamate receptor 5 in opposite directions, and deficits in the mutants disappear when the mice are bred to carry both mutations. Thus, normal synaptic plasticity and cognition occur within an optimal range of metabotropic glutamate-receptor-mediated protein synthesis, and deviations in either direction can lead to shared behavioural impairments.National Institute of Mental Health (U.S.) (T32 MH-082718)National Institute of Mental Health (U.S.) (T32-MH-074249)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (2R01HD046943)United States. Dept. of Defense (W81XWH-11-1-0252)Simons Foundatio

Lifting the Mood on Treating Fragile X

Only a decade ago, it was believed that a genetic diagnosis of intellectual disability and autism offered little in the way of hope for a medical treatment to lessen the burden on the affected individuals and their families. However, recent research aimed at understanding the cellular and molecular mechanisms that underlie the pathogenesis of ASD has ushered in a new era of targeted treatment strategies. Studies in fragile X syndrome (FXS) have been at the forefront of this revolution, and they are forging a path that could define future approaches to the treatment of ASD

Recovery From Monocular Deprivation Using Binocular Deprivation: Experimental Observations and Theoretical Analysis

Ocular dominance (OD) plasticity is a robust paradigm for examining the functional consequences of synaptic plasticity. Previous experimental and theoretical results have shown that OD plasticity can be accounted for by known synaptic plasticity mechanisms, using the assumption that deprivation by lid suture eliminates spatial structure in the deprived channel. Here we show that in the mouse, recovery from monocular lid suture can be obtained by subsequent binocular lid suture but not by dark rearing. This poses a significant challenge to previous theoretical results. We therefore performed simulations with a natural input environment appropriate for mouse visual cortex. In contrast to previous work we assume that lid suture causes degradation but not elimination of spatial structure, whereas dark rearing produces elimination of spatial structure. We present experimental evidence that supports this assumption, measuring responses through sutured lids in the mouse. The change in assumptions about the input environment is sufficient to account for new experimental observations, while still accounting for previous experimental results